The objective of this study is to examine mechanisms by which the immune system can influence transformation and growth of human lymphoid malignancies. Two models have been pursued: (1)\the analysis of identity and function of membrane proteins defining subsets of patients with hairy cell leukemia; and (2)\study of antibody-mediated mechanisms influencing transformation induced with Epstein-Barr virus (EBV). In the study of hairy cell leukemia, we have defined subsets of patients on the basis of enhanced expression of 35,000-\and 15,000-dalton microsomal membrane-associated proteins. By two-dimensional gel electrophoresis of membrane preparations and immunoprecipitations with several antisera, p35 was demonstrated to be the human analog of murine Ii, a structurally invariant molecule associated with Ia antigens. Current objectives include: (1)\production of panels of monoclonal antibodies to Ii; (2)\distribution and quantitation of Ii on leukemic cells; and (3)\function of Ii in processing of Ia to the cell surface and/or in regulating Ia function on normal and leukemic cells. The second path of effort lies in characterizing humoral influences upon transformation of lymphoid cells by EBV. We have defined antibody-induced suppression of EA expression in 48-hour P3HR-1-EBV-superinfected Raji cells. Since this effect is phosphonoacetic acid sensitive, one can hypothesize that the effect is probably mediated by an antibody to a late membrane antigen. Our goal is to produce monoclonal antibodies which mediate this effect in order to: (1)\quantitate its kinetics; (2)\evaluate the clinical relevance of the effect; and (3)\determine whether the antibody potentiates latency of EBV.